Starvation hormone makes for small mice

June 26, 2008

Chronically high levels of a recently discovered starvation hormone markedly stunt the growth of mice, reveals a new study in the July issue of Cell Metabolism, a publication of Cell Press. The liver-produced hormone known as FGF21 does so by causing the mice to become resistant to growth hormone.

"It was an unexpected finding," said David Mangelsdorf of University of Texas Southwestern Medical Center. "In starvation, [it was known that] growth hormone goes down. This might explain much of the mechanism responsible."

The researchers showed in another Cell Metabolism report last year that FGF21 shifts the metabolism of mice to a fat-burning mode and induces a state of energy-conserving torpor. FGF21 has since been shown to act as an insulin sensitizer, as well.

The new findings uncover an even broader physiological role for the hormone in promoting energy conservation when animals go without food, said Mangelsdorf and study coauthor Steven Kliewer, also of the University of Texas Southwestern Medical Center.

They report that mice with higher-than-normal levels of FGF21 are normally sized at birth, but they gain less weight and their bones grow less. That's despite the fact that the animals eat more relative to their body weight than control mice do.

Further study showed that FGF21 reduced concentrations of a growth hormone-mediating transcription factor (a gene that controls the activity of other genes), leading to a decline in the expression of its target genes, including insulin-like growth factor 1 (IGF-1).

The earlier discovery of FGF21's effects on fat metabolism and insulin response have led to considerable interest in its potential use as a type 2 diabetes drug, Mangelsdorf said. Therefore, it will be important to understand what else the hormone might do.

On the plus side, FGF21's growth hormone actions, along with its insulin effects, support the notion that it might extend life span, a hypothesis Mangelsdorf and Kliewer's team intends to explore. On the other hand, chronically blocking growth hormone could have other ill effects.

The new results might also explain the action of fibrate drugs now in use for treating patients with metabolic syndrome, Mangelsdorf said. Those drugs target a receptor known as PPARa, which is necessary for rise in FGF21 that occurs in fasted mice.

Notably, in clinical studies, the PPARa-agonist bezafibrate significantly lowers IGF-1 levels in patients," the researchers said. "This finding together with data showing that FGF21 expression is induced by PPARa agonists in primary human [liver cells] suggest that the PPARa/FGF21 pathway may be operative and affect IGF-1 signaling in humans."

Omega-3 fatty acids are able to stimulate the activation of brown and beige adipose tissues, a discovery that would promote the development of new therapies for obesity and other metabolism diseases, according to a research ...

A compound found in breast milk, named fibroblast growth factor 21 (FGF21), plays a key role in neonatal nutrient absorption and intestinal function. FGF21 also contributes to improve newborn growth and metabolic profile.

Recommended for you

Short telomeres—the protective caps on the ends of chromosomes—have been previously linked to increased risk of death from heart disease. Now, research by scientists at UC San Francisco and the Veterans Affairs Medical ...

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

A team of scientists has uncovered details of the cellular mechanisms that control the direct programming of stem cells into motor neurons. The scientists analyzed changes that occur in the cells over the course of the reprogramming ...

Researchers from the University of Pittsburgh School of Medicine and UPMC have engineered a protein that reverses carbon monoxide (CO) poisoning in mice, a discovery that could potentially lead to the creation of the first ...

0 comments

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.